tbuckley/cabot-search huggingface dataset:
P03.15.B SURGICALLY TARGETED RADIATION THERAPY (START) FOR RECURRENT GLIOBLASTOMA: INITIAL OUTCOMES FROM A PROSPECTIVE MULTICENTER REGISTRY
Authors: A Ozair, C Shen, S Lee, H Pham, R Chamoun, O Choutka, S Hanft, M Shah, A Richardson, V DiNapoli, Z Wardak, C Ferreira, A A Khosla, K Bojanowski-Hoang, C E Mercado, R Ryan, A Wasilewski, D Brachman, L Campbell, C Chen, K Dusenbery, J Floyd, T Patel, D Hayden, A Nowlan, D McCracken, J Wanebo, T Ranjan, A Rodriguez, A J Patel, P J Camarata, R R Kotecha, M W McDermott, M S Ahluwalia
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Surgically targeted radiation therapy (STaRT), using a novel bioresorbable collagen brachytherapy device containing 4 Cesium-131 sources, is FDA-cleared for use as adjuvant radiation therapy (RT) post-resection in both newly diagnosed and recurrent intracranial neoplasms. Intraoperative initiation of brachytherapy potentially minimizes post-resection tumor regrowth with a favorable dosimetric profile compared to external beam radiation. This work sought to determine early patterns of care and the safety of this approach in recurrent glioblastoma (GBM). MATERIAL AND METHODS This prospective multi-institutional observational study (NCT04427384) included recurrent GBM patients who underwent maximum safe resection (MSR) and permanent implantation of the device(s) (GammaTile, GT Medical Technologies, Tempe, AZ, US). Descriptive and comparative analyses regarding patient characteristics and early clinical outcomes were performed. Toxicities were categorized using the CTCAE v5.0 adverse event (AE) criteria. RESULTS During 10/2020-01/2023, 14 participating sites enrolled 45 patients with recurrent GBM for STaRT; 2 patients had two sites treated for a total of 47 implants. 67% of patients were treated at the first recurrence, 24% at the second, and 13% at the third, respectively. The median age was 61 (range 28-75), 36% were female, and 23% were &amp;gt;65 years. 85% of patients received prior same-site RT with the median time from last RT to implantation of 14.6 months (range 3.5-57). The median maximum preoperative size was 4.2 cm (range 1.6-7.0), and the median volume was 20.8 cm3 (range 0.8-130). 68% of resections were gross-total, 17% near-total, and 15% sub-total; the median time needed for device implantation was 5 minutes (range 1.0-13). Median follow-up was 5.2 months (range 0.6-23.2). Median Karnofsky performance status (KPS) at screening, at initial postoperative assessment, and 3 months were all 80 (range 40-100). 7 attributed AEs occurred in 13% (6/45) of patients, all grade 3 AEs: 2 CSF leaks, 2 seizures, 1 cerebral edema, 1 pseudomeningocele, and 1 left hemiparesis. All except one were coded as related to both radiation and surgery; the patient with pseudomeningocele experienced a seizure at 47 days that was considered related to radiation alone. CONCLUSION Early data from this prospective registry demonstrate the feasibility and safety of STaRT in recurrent GBM. Data on 6-month progression-free survival will be presented at the conference. A prospective randomized trial of adjuvant systemic therapy (AST)+MSR+STaRT versus MSR+AST is planned for initiation in 2023.
P11.17.A TEMOZOLOMIDE ONLY FOR GBM MGMT PROMOTER METHYLATEDELDERLY PATIENTS IN REAL CLINICAL SET
Authors: E Falah, O Furman, O Haisraely, N Atar is, E Jan, L Zach, A Taliansky
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The course of glioblastoma (GBM) is worse in elderly and low KPS patients. The NORDIC and NOA08 clinical trials proved the non-inferiority of temozolomide (TMZ) treatment to radiotherapy alone for GBM MGMT promoter methylated (MGMT MET) elderly patients. TMZ alone is thus recommended in guidelines as first line of treatment for this group of patients. The data of real life efficacy of this treatment are sparse. MATERIAL AND METHODS We retrospectively evaluated the data of GBM MGMT MET patients, older than 65y that were treated in the Neuro-oncology unit at Sheba MC during 2012-2022. The treatment was adjuvant TMZ 200mg/m2/day 5 days q28 days. We compared treatment outcomes in our patients to the results of the NORDIC and NOA08 RCTs. RESULTS 36 patients were included in our analysis with stereotactic biopsy for diagnosis in 47% of them: 34 patients had GBM, 1 had WHO grade 3 Astrocytoma and in 1 patient the diagnosis was made by imaging (non diagnostic biopsy). Of this group, 25 were males and 11 females. The mean age was 76y (64-90) and 96% had KPS ≤ 60. Only one patient had IDH 1 mutation and in 9 cases IDH status was unknown. The interval from diagnosis to treatment was 2-19 weeks (median 6 weeks). The number of TMZ cycles was 1-12 (mean of 4 cycles after the exclusion of 11 patients who received less than 3 cycles). Median PFS/OS was 3 /7.5 months and 5/11 months respectively for the whole group and for patients that received ≥3 cycles. The 12/18/24 months survival rate was 33%/13%/8% respectively. 21 patients received second line treatment: 13 radiotherapy, 1 TMZ re-challenge and 7 Bevacizumab. Eight patients received a third line of treatment: 2 radiotherapy, 4 Bevacizumab, 1 Procarbazine and 1 TMZ. Grade 3-4 hematological toxicity was documented in 20% of the patients, with infections in 12.5% and bleeding in 4%. Fatigue was reported in 17% of the patients. CONCLUSION While our patients were older and with lower KPS than the patients in the RCTs the efficacy of TMZ only treatment was comparable with the clinical trials results with mOS of 11/11.9/8.3 month in Sheba/NOA08/Nordic patients, PFS of 5/8.4/NA in Sheba/NOA08/Nordic patients respectively. The main toxicity reported in all 3 data sets was hematological 20%/38%/12% in Sheba/NOA08/Nordic patients. We can conclude that TMZ only for GBM MGMT MET elderly patients in real clinical set is a valuable and safe first line treatment. &amp;lt;!--EndFragment--&amp;gt;
P14.01.A LIQUID BIOPSY OF GLIOMA-RELATED GENES USING A NOVEL AMPLIFICATION TECHNIQUE
Authors: J Adachi, T Suzuki, R Nishikawa
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND In the pathological classification of brain tumors, newly revised in 2021, molecular genetic analysis of gliomas has become more important for diagnosis and understanding of the pathogenesis of gliomas. Gliomas are prone to recurrence and malignant progression, and collecting tumor tissue during every genetic analysis is highly invasive. Therefore, techniques have been developed to analyze tumor-derived circulating cell-free DNA (ccfDNA) in the cerebrospinal fluid as a substitute for tissue collection. However, the amount of ccfDNA derived from the cerebrospinal fluid is extremely small and the number of cases for whom genetic analysis is possible is currently limited. In this study, we attempted to establish a novel method for the integrated analysis of glioma-related genes by in vitro amplification of cerebrospinal fluid-derived ccfDNA from glioma patients and a highly sensitive assay. Methods : Tumor-derived ccfDNA was extracted and purified from 1 ml of cerebrospinal fluid obtained by lumbar puncture using the Maxwell RSC instrument in five glioma cases. Hot spots of mutations in IDH1 and H3F3A genes were analyzed by high resolution melting (HRM), TERT mutation by droplet digital PCR, MGMT promoter methylation by methylation-specific HRM, and chromosome 1p/19q loss by multiplex ligation-dependent probe amplification. For samples in which the amount of ccfDNA was too small to analyze, DNA was amplified approximately 500-fold by DNA polymerase using the GenomiPhi kit and analyzed by the same assay method. Results and CONCLUSION s : Although two of the five cases required amplification with the GenomiPhi kit, it was possible to analyze all cases for glioma-related genes as described above. Although the amount of ccfDNA obtained from low-grade gliomas and gliomas that are not in contact with the ventricles or subarachnoid space is small, this amplification method may increase the possibility of liquid biopsy using cerebrospinal fluid in gliomas.
P11.48.A STEREOTACTIC RADIOSURGERY FOR EPENDYMOMA IN PEDIATRIC AND ADULT PATIENTS: A SINGLE-INSTITUTION EXPERIENCE
Authors: K H Yoo, N J Marianayagam, D J Park, A Zamarud, X Gu, E L Pollom, S G Soltys, S D Chang, A Meola
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Ependymoma is typically classified as WHO grade 2 and its anaplastic variant as grade 3. Despite standard treatment approaches, incomplete resection or anaplastic features can lead to poor prognosis. Stereotactic radiosurgery (SRS) is a promising minimally invasive option for recurrent ependymomas after surgery and radiation therapy. This study aims to evaluate the efficacy and safety of CyberKnife radiosurgery in treatment of WHO grade II versus III ependymomas in both pediatric and adult populations. MATERIAL AND METHODS In our study, we evaluated the clinical and radiological records of patients who underwent CyberKnife SRS for ependymoma at our institution between 1998 and 2023. The follow-up data were available for a total of 75 ependymomas in 34 patients. The study population consisted of 14 pediatric patients (ages 3-18) and 20 adult patients (ages 19-75). The median age was 21 years and the median tumor volume accounted for 0.64 cc. The median biologically equivalent dose (BED) and single-fraction equivalent dose (SFED) were 108 Gy and 16.6 Gy, respectively. The SRS was administered at the 77% of the median isodose line. RESULTS At a median follow-up of 42.7 months (range: 3.8-438.3) after treatment, our analysis revealed that only 17 (22.7%) ependymomas progressed. The 5-year local tumor control (5-yrs-LTC) rate for all ependymomas was 78.1%, with a lower rate of 59.6% observed in the pediatric cohort and a higher rate of 90.2% in adult patients. For ependymomas classified as WHO grade II, the 5-yrs-LTC rate was 85.9%, whereas it was 58.5% for those classified as WHO grade III. The 5-year overall survival (5-yrs-OS) rate was 73.6% for all patients, with significantly higher rates observed in pediatric patients (94.7%) than in adult patients (41%). The 5-yrs-OS rate was 100% for patients with WHO grade II tumors, whereas it decreased significantly to 35.9% for patients with WHO grade III ependymomas. The 5-year progression-free survival (5-yrs-PFS) rate was 68.5% for all patients, with higher rates observed in pediatric patients (78.3%) than in adult patients (49.2%). The 5-yrs-PFS rate for patients with WHO grade II lesions was 88.8%, whereas it was significantly lower at 32.6% for patients with WHO grade III tumors. Stereotactic radiosurgery (SRS) was effective in improving tumor-associated symptoms in 29 (85.3%) patients with 62 (82.7%) symptomatic ependymomas. These symptoms included headache, back pain, dizziness, nausea, vomiting, cranial nerve palsy, ataxia, motor impairment, sensory deficit, seizures, and weight loss. Notably, no patients developed adverse radiation effects. CONCLUSION CyberKnife SRS is a safe and effective treatment for ependymoma in both adults and children, with potential for significant improvements in tumor-related symptoms. Our study supports its use as a minimally invasive alternative to surgery, warranting further investigation.
P03.09.B LOW DOSE BATH FROM RADIOSURGERY TO SURROUNDING NORMAL BRAIN IN TREATMENT OF BRAIN METASTASES COULD STERILIZE BRAIN AND INHIBIT RECURRENCES
Authors: T Mader, S Bhutto, J Tranter, L F Martins Gomes, M Hawkins, A Spyridonidis, B G Baumert
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) are standard treatments for brain metastases. Each SRS/fSRT plan has a low-dose penumbra outside the high dose area, which multiplies if multiple metastases are irradiated and results in a low-dose bath in healthy brain tissue. We hypothesize that a certain dose of the low-dose bath can sterilize brain tissue and prevent local recurrences. We present first data of an ongoing project. MATERIAL AND METHODS Data of fifty-three patients with brain metastases treated with single fraction SRS or fractionated fSRT at our institute between 2020 and 2022 were reviewed retrospectively. All patients with at least one cranial follow-up MRI after 3 months were evaluated. Follow-up MRI scans were fused to the original treatment plans. New metastases in the isodose-volumes of 10 Gy-, 8 Gy-, 6 Gy-, 4 Gy-, and 2 - Gy were identified and evaluated. Mean doses, on the site of the new lesions, received from SRS/fSRT were tabulated summarized and analyzed. RESULTS Six of the 53 patients met the inclusion criteria. Five patients developed recurrent brain metastases out-of-field within 2-4 months of follow-up. One metastasis was observed outside the irradiation field. One patient developed no new metastases. With decreasing isodose levels an increasing number of new metastases were observed: In the reconstructed volume of 10Gy (V10Gy), V8Gy and V6Gy two metastases each, no metastases in the V4Gy and 5 metastases in the V2Gy. No toxicities were observed. CONCLUSION Our data suggest a trend towards a benefit that the low-dose bath as part of the penumbra of stereotactic radiotherapy sterilizes brain tissue. Especially, brain regions receiving doses of 4 Gy or more had fewer new lesions compared to regions that received less than 4 Gy. This should be further validated prospectively in larger patient populations, in clinical trials with combination of CNS-accessible immunotherapy like Osimertinib. Indications for whole brain radiotherapy could be further reduced. Low dose spillage with manageable risks might be sufficient to treat microscopic brain metastases in the future.
P09.07.A SYMPTOM AND DISTRESS IN PATIENTS WITH MALIGNANT BRAIN TUMOR TREATED WITH PROTON BEAM THERAPY. A FIVE-YEAR FOLLOW-UP STUDY
Authors: K Kunni, U Langegård, P Fransson, T Proton Care Study Group
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Due to new treatment regimes, an increasing proportion of patients with malignant brain tumors will likely be long-term survivors. To ensure optimal care for this patient group, it is crucial to conduct further research, including long-term follow-up of treatment-related symptoms, and distress. Patients with malignant brain tumors experiencing distressing symptoms will result in poorer overall survival and decreased quality of life. Despite this, the correlation between symptoms and distress in adults with malignant brain tumors undergoing proton beam therapy remains poorly understood. This study aimed to explore if symptoms and distress change over five years in adults with malignant brain tumors treated with proton beam therapy. An additional aim was to explore if symptoms and distress correlate. MATERIAL AND METHODS The study had a quantitative longitudinal multicenter design.Adult (≥18 years) patients (n = 149) with malignant brain tumors treated with proton beam therapy were followed over five years. The degree of symptom and distress were evaluated using the patient-reported Radiotherapy-Related Symptom Assessment Scale. Data from baseline, 1, 12-, and 60 months were analyzed using non-parametric tests. The correlation between symptoms and distress were analyzed using Spearman’s correlation. RESULTS Levels of symptoms and distress were generally low. Fatigue had the highest levels at all timepoints. Cognitive impairment increased significantly at 12-months (P=0.002) and was the most distressing symptom at 60-months follow-up. The results showed a significant, moderate to strong, correlation at all time points between symptoms and distress of fatigue, insomnia, pain, cognitive impairment, worry, anxiety, nausea, sadness, and skin reactions. CONCLUSION Our study highlights the correlation between symptoms and distress in adults with malignant brain tumors treated with proton beam therapy. Further, this study emphasizes that nursing should focus on what patients experience as the most distressing symptoms. Research should identify effective interventions to alleviate symptoms and reduce patient distress. Given the significant correlation between symptoms and distress in our study, we suggest developing cancer rehabilitation. Reduced levels of distressing symptoms would lead to a better quality of life and increased survival for this vulnerable group of patients.
P10.12.B MOLECULAR MECHANISMS INVOLVED IN THE DEVELOPMENT OF BRAIN METASTASIS FROM THE MATCHED PAIRED LUNG ADENOCARCINOMA AND BREAST CANCER
Authors: S Najjary, J M Kros, W de Koning, D A M Mustafa
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Up to 50% of patients with common cancers will develop brain metastases and incidences of this devastating complication are still rising. In our recent work, we found that the immune response in the brain is significantly stronger when the metastasis develops from lung adenocarcinoma (LUAD) compared to breast cancer (BC). Importantly, we discovered the higher expression of the drug target, VISTA, only in the brain metastasis of the LUAD. The aim of the current study was to investigate the molecular mechanisms driving the formation of brain metastasis from the two different lineages of cancer. In addition, we aimed to examine the expression level of the drugable molecules between primary tumors and their brain metastasis. MATERIAL AND METHODS Primary tumor and their matched brain metastasis samples of 11 LUAD and 11 breast cancer (total = 44 samples) were included in this study. RNA was extracted from the FFPE samples and the targeted gene expression profiles were measured using the PanCancer IO360™ Panel that includes 770 cancer-related genes (NanoString technology). Data were analysed using the nSolver software. RESULTS A first comparison was made between the primary tumors with their brain metastases for LUAD and BC separately. The second comparison was made between the common genes of both lineages. Pathway analysis indicated that there is higher metabolic stress in breast cancer-brain metastasis compared to that in the lung. In addition, we identified 12 common up-regulated genes in brain metastasis, despite the origin of the primary tumor. Importantly, by comparing the primary tumors of BC and LUAD with their brain metastasis, we found that VISTA is predominantly highly expressed in the primary tumors of LUAD and their matched brain metastasis. CONCLUSION Although the general mechanisms of metastasis have been described, our study demonstrates that different cancer lineages utilize various genes/pathways to metastasize to the brain. Moreover, primary LUAD and their brain metastasis express high levels of VISTA highlighting the possibilities for targeted therapy.
P10.26.B EXPLORING POTENTIAL ANTITUMOR EFFECTS OF CANNABIDIOL AND TETRAHYDROCANNABINOL IN A PATIENT-DERIVED GLIOBLASTOMA MODEL
Authors: S Zekanovic, M J van den Bent, C M F Dirven, M L M Lamfers, S Leenstra
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Glioblastoma (GBM) is a CNS malignancy which is in dire need of novel treatment options. Drug repurposing has become a means to circumvent major obstacles that accompany drug development for GBM. The cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) have garnered the interest of the scientific community for the treatment of GBM as they possess pleiotropic effects in other pathologies. In the present study we are investigating potential antitumor effects of these cannabinoids by using our patient derived GBM model which recapitulates GBM in its genetic make-up and heterogeneity. MATERIAL AND METHODS To assess potential antitumor effects in vitro, we performed a screen on 20 patient derived GBM cultures to obtain a sensitivity profile for both cannabinoids. These cultures ranged in background regarding primary/recurrence and IDH mutation. To investigate effects of these cannabinoids on GBM radio-and-chemosensitivity, combination studies with either lomustine (CCNU) or irradiation (RTx) were performed on recurrent GBM cultures. The zero-interaction potential method was used to quantify synergy between the cannabinoids. The enhancement factor was used to quantify potential radiosensitization or ratio-effects between the cannabinoids. RESULTS Screening of both cannabinoids revealed CBD to possess a higher level of cytotoxicity than THC. IC50 values of CBD ranged from 2.5 - 18.5 µM and the values of THC ranged from 7.20 - 47.60 µM. In a panel of 8 cultures, combinations of CBD with THC, CBD with CCNU and THC with CCNU was tested to gain insight in combination effects. In 1/8 cultures synergy was observed between CBD and THC. In 1/8 cultures synergy between CBD and CCNU was observed and in 4/8 cultures synergy between THC and CCNU. When combined with irradiation, no enhancement was observed in any of the 4 cultures tested. No ratio-dependent enhancement between the cannabinoids was observed when combined in a 1:1, 1:4 or 4:1 ratio of CBD:THC. CONCLUSION Screening of the cannabinoids CBD and THC revealed that CBD displays a stronger cytotoxic effect than THC. Combinations of either of the two with each other or CCNU revealed moderate additive effects in the majority of cultures and synergy in a small subset. We did not observe radiosensitizing effects in our patient derived GBM model. Relating in vitro found cytotoxic concentrations to clinically achievable concentrations, we found that CBD requires approximately 3 times higher plasma concentrations and THC &amp;gt;40 times to achieve an antitumor effect. Currently we are investigating long term treatment effects of CBD and its mechanism of action.
P13.08.A JAKOB V. E. GERSTL, MBBS
Authors: J V E Gerstl, C A G von Grothusen, J L Kilgallon, R Lindberg, J Onnela, T R Smith
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Pituitary adenomas are benign neoplasms which can have a profound impact on quality of life. In-situ assessments of patient quality of life with pituitary adenomas and recovery from surgery are limited; existing patient reported outcome measures are, moreover, biased by patient recollection. Smartphone-based digital phenotyping may provide a means of monitoring patient recovery and quality of life at a more granular and accurate level. MATERIALS AND METHODS Patients with pituitary adenomas were enrolled during preoperative clinic visits. Included patients installed the Beiwe application, which passively collected GPS data during patient follow-up. Dates of significant clinical events were recorded to assess how they affected mobility. Using a LOESS regression line, aggregate trends amongst patients who underwent transsphenoidal resection were established and compared to baseline values from preoperative patients awaiting surgery and non-operative controls. RESULTS As part of a still ongoing study, 35 Patients with pituitary adenomas were enrolled between October 2022 and February 2023. Of these, 13 underwent transsphenoidal resection, the remaining 22 patients were either waiting for surgery and/or served as non-operative controls. Patients undergoing transsphenoidal resection of pituitary adenomas spent more time at home, spent less time walking, walked fewer steps and traveled shorter distances away from home compared following surgery compared to baseline preoperative data and non-operative controls. CONCLUSION The authors were able to generate initial digital phenotypes for a cohort of pituitary patients based on passively collected smartphone GPS data; the authors also hope that these initial data may help in the establishment of an in-situ tool to monitor recovery following surgery for pituitary adenoma. It is the authors’ contention that such preoperative mobility metrics may be further utilized to predict postoperative outcomes following surgery which has been demonstrated in the general surgery setting. In the case of pituitary disease, these include postoperative CSF leak, infection, dysnatremia and hospital length of stay.